The ultimate goal of our studies is to understand in molecular terms how bacteria cause diseases. A bacterial infection can be regarded as a war between the microbe and the host where the bacteria's attempt to adhere to and colonize the host tissue represent the first battle in the campaign. For our model organism, Staphylococcus aureus tissue adherence is mediated by a sub-family of bacterial surface adhesins called MSCRAMMs. In previous work, we discovered the MSCRAMMs, cloned and sequenced several MSCRAMM genes and began characterizing the encoded proteins and their interactions with host components. These studies revealed amazingly sophistical mechanisms of host tissue adherence designed to avoid inactivation by host defense systems. We hypothesize that the MSCRAMMs are in the first line of bacterial attachment and their molecular design makes them uniquely suited for this role. Consequently, we now propose a detailed molecular analysis of Staphylococcal surface proteins and their interactions with host components.